1 / 76

הוראה בנושאי טיפול תרופתי בסרטן

הוראה בנושאי טיפול תרופתי בסרטן. מאמרי מפתח, קווים מנחים וסקירות נבחרות החל משנת 2000 ערך: פרופ’ נ. חיים , מאי 2004 , עודכן: מרץ 2007 המצגת אינה מעודכנת כתובת לשאלות והערות: n_haim@rambam.health.gov.il. CTCAE [formerly known as CTC (CommonToxicity Criteria)]….

bandele
Download Presentation

הוראה בנושאי טיפול תרופתי בסרטן

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. הוראה בנושאי טיפול תרופתי בסרטן מאמרי מפתח, קווים מנחים וסקירות נבחרות החל משנת 2000 ערך: פרופ’ נ. חיים , מאי2004 , עודכן: מרץ 2007 המצגת אינה מעודכנת כתובת לשאלות והערות: n_haim@rambam.health.gov.il

  2. CTCAE [formerly known as CTC (CommonToxicity Criteria)]…..

  3. CTCAE [formerly known as CTC (Common Toxicity Criteria Common Toxicity Criteria)] • http://ctep.cancer.gov …..CTCAE (formerly known as CTC) v2.0 and v3.0 (v3.0 – publish date: December 12, 2003)

  4. Chemotherapy-induced nausea and vomiting • Recent guidelines…. • NK1 receptor antagonists…. • ראה מצגת "מנגנוני פעולה ועמידות של תרופות ציטוטוקסיות ו”תרופות מגינות” לגבי מנגנון פעולה של התרופות השונות.

  5. Chemotherapy-induced nausea and vomiting-Recent guidelines • 1. Perugia International Cancer Conference VII- MASCC (Multinational Association of Supportive Care in Cancer) www.mascc.org(last update: Sept 2005) See also: The Antiemetic Subcommittee of the Multinational Association of the Multinational Association of Supportive Care in Cancer (MASCC). Ann Oncol 17: 20-8, 2006. • 2. ASCO Guidelines Kris MG et al. J Clin Oncol 24: May 22, 2006 (published ahead of print) • 3. National Comprehensive Cancer Network (NCCN) http://www.nccn.org ---see: Clinical Practice Guidelines in Oncology-v. 1. 2007----see: Antiemesis

  6. NK1 receptor antagonists • de Wit R et al. Addition of the oral NK1 antagonist Aprepitant to standard antiemetics provided protection against nausea and vomiting during multiple cycles of cispltin-based chemotherapy. J Clin Oncol 21: 4105-11, 2003 • Hesketh PJ et al. The oral neurokinin-1 antagonist Aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational , randomized , double-blind, placebo-controlled trial in patients receiving high-dose cisplatin-the Aprepitant Protocol 052 Study Group. J Clin Oncol 21: 4112-19, 2003 • Kris MG. Why do we need another antiemetic? Just ask. J Clin Oncol 21: 4077-80, 2003 (editorial)

  7. Chemotherapy and radiotherapy protectants • ASCO guidelines for the use of mesna, dexrazoxane,and amifostine …. • ראה מצגת "מנגנוני פעולה ועמידות של תרופות ציטוטוקסיות ו”תרופות מגינות” לגבי מנגנון פעולה של התרופות השונות.... • ראה מצגת "פרמקוקינטיקה ומטבוליזם..." לגבי צורות מתן של mesna. • ראה גם: המלצות החוג לכימותרפיה למעקב לבבי בחולים המטופלים עם אדריאמיצין ומניעתה ע"י דקסרזוקסן ב: www.iscort.org.il

  8. Chemotherapy and radiotherapy protectants-ASCO Guidelines Schuchter LM et al. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 20: 2895-2903, 2002 : Guidelines for the use of mesna, dexrazoxane, and amifostine….

  9. ASCO recommendations on fertility preservation in cancer patients

  10. ASCO recommendations on fertility preservation in cancer patients Lee SJ et al. J Clin Oncol 24: 2917-31, 2006

  11. GCSF & Feblile neutropenia • NCCN Guidelines…. • ASCO Guidelines (GCSF)…. • EORTC Guidelines…. • 2002 guidelines of the Infectious Diseases Society of America (IDSA) & Fever and Neutropenia Guidelines Panel…. • Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas…. • ראה גם מצגת "מנגנוני פעולה של תרופות ציטוטוקסיות ותרופות מגינות" • ראה גם: המלצות החוג לכימותרפיה לטיפול בגורמי צמיחה של השורה הלבנה ב: www.iscort.org.il

  12. GCSF- NCCN, ASCO & EORTC Guidelines • NCCN: Clinical Practice Guidelines in Oncology / Myeloid Growth Factors in Cancer Treatment / Version 1. 2007 http://www.nccn.org • ASCO: 2006 Update of recommendations for the use of white blood cell growth factors: an evidence-based, clinical practice guidelines. Smith TJ et al. for the American Society of Clinical Oncology Growth Factor Expert Panel. Published ahead of print on J Clin Oncol May 8, 2006 • EORTC: EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia adult patients with lymphomas and solid tumors. Aapro MS et al. Published ahead of print, Europ J Cancer , 2006

  13. 2002 guidelines of the Infectious Diseases Society of America (IDSA) & Fever and Neutropenia Guidelines Panel • Hughes WT et al. Clin Infect Dis 34: 730-51, 2002

  14. Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas • Cullen M et al. N Engl J Med 353: 988-98, 2005 Pts treated with chemo protocols associated with severe neutropenia, but not routinely treated with GCSF, were randomized to receive levofloxacin or placebo for 7 days to cover the the period of anticipated neutropenia. The prophylactic use of levofloxacin reduced the incidence of fever, probable infection, and hospitalization.

  15. Epoeitin • ASCO/ASH Guidelines…. • EORTC Guidelins…. • NCCN Guidelines….

  16. Epoeitin-ASCO & EORTC & NCCN Guidelines • Rizzo JD et al. Use of Epoeitin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 20: 4083-4107, 2002: Guidelines for the use of epoietin in patients with chemotherapy induced anemia…. • Bokemeyer C et al. EORTC guidelines for the use of erythropoietic proteins in anemic patients with cancer. Eur J Cancer 40: 2201-16, 2004 • Guidelines for the use of epoietin in anemic cancer patients…. NCCN Clinical Practice Guidelines in Oncolgy. Cancer-and Treatment-Related Anemia. Version 1. 2007www.mascc.org

  17. Recommended guidelines for the treatment of cancer chemotherapy-induced diarrhea • Independent panel (mortality associated with IFL)… • Panel recommendations…. ראה גם: המלצות החוג לכימותרפיה לטיפול בשלשול כתוצאה מכימותרפיה-תת אתר החוג לכימותרפיה ב: www.iscort.org.il

  18. Independent panel-mortality associated with IFL • Rothenberg ML et al. Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 19: 3801-7, 2001: Guidelines suggested after a report of high mortality rate associated with the “Saltz regimen”.

  19. Recommended guidelines for the treatment of cancer chemotherapy-induced diarrhea • Benson III Al B et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22: 2918-26, 2004: Guidelines of an independent panel of experts. Includes also guidelines for radiotherapy-induced diarrhea). See also previous panel recommendations(Wadler S et al. Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 16: 3169-3178, 1998)

  20. Extravasation of cytotoxic agents • ראה גם: המלצות החוג לכימותרפיה למניעה וטיפול בדליפה מחוץ לווריד של תרופות צחטוטוקסיות ב: www.iscort.org.il

  21. Extravasation of cytotoxic agents • Ener RA et al. Extravasation of systemic hemato-oncological therapies. Ann Oncol 15: 858-62, 2004: …includes background and suggested guidelines.

  22. Chemotherapy sensitivity and resistance assays • ASCO assessment….

  23. Chemotherapy sensitivity and resistance assays: ASCO assessment • Schrag D et al. American Society of Clinical Oncology technology assessment: chemotherapy sensitivity and resistance assays. J Clin Oncol 22: 3631-8, 2004: “The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside the clinical trial setting.” See also a systematic review: Samson DJ et al. J Clin Oncol 22: 3618-30, 2004: “ ….These results do not establish the relative effectiveness of assay-guided treatment and empiric treatment”.

  24. Thalidomide • Mechanism of action, side effects, current role in solid tumors….

  25. Thalidomide: Mechanism of action, side effects, current role in solid tumors • Kumar S et al. J Clin Oncol 22: 2477-88, 2004 (review) and/or: Eleutherakis-Papaiakovou V et al. Ann Oncol 15: 1151-60, 2004 (review)

  26. Somatostatin analogs • Consensus report of the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system….

  27. Somatostatin analogs • Oberg K et al. Consensus report of the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 15: 966-73, 2004 A consensus report on the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system.

  28. Bisphosphonates • ASCO Guidelines….

  29. Bisphosphonates-ASCO Guidelines • Hillner BE et al. American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer. J Clin Oncol 21: 4042-57, 2003 Schedule of administration of pamidronate, and zoledronic acid; guidelines for administration in patients with renal dysfunction…. see also previous version:J Clin Oncol 18: 1378-91, 2000.

  30. Brain Tumors • Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma….

  31. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma • Stupp R et al. N Engl J Med 352: 987-96, 2005: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in clinically meaningful and statistically significant survival benefit with minimal additional toxicity.

  32. Breast cancer • Dose-dense vs. conventional AC/taxol as adjuvant in node-positive breast cancer…. • Adjuvant docetaxel for node-positive breast cancer (TAC vs. FAC)…. • ATAC…. • Letrozole vs tamoxifen as adjuvant….. • adjuvant hormone therapy beyond tamoxifen: - Exemestane after 2 to 3 years of tamoxifen in post menopausal women…. - Anastrazole after 2-3 yrs of tamoxifen…. • - Letrozole after 5 years of tamoxifen…. • Herceptin with chemotherpy and as single agent ….. • Herceptin every 3 weeks…. • Herceptin as adjuvant…. • HER2 and responsiveness of breast cancer to adjuvant chemo…. • ASCO technology assessment of the use of aromatase inhibitors….

  33. Dose-dense vs. conventional AC/taxol as adjuvant in node-positive breast cancer • Citron ML et al. J Clin Oncol 21: 1431-39, 2003 • See also editorial: Piccart-Gebhart MJ, Mathematics and oncology: a mach for life? J Clin Oncol 21: 1425-8, 2003 (editorial) • The dose-dense arms improved DFS; severe neutropenia was less frequent in pts treated with the dose-dense regimens.

  34. Adjuvant docetaxel for node-positive breast cancer (TAC vs. FAC) • Martin M et al. N Engl J Med 352: 2302-13, 2005 Adjuvant chemo with TAC, as compared with FAC, significantly improves the rates of disease-free and overall survival among women with operable node-positive breast cancer.

  35. ATAC study • Atac Trialists’ Group. Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet December 8, 2004

  36. Breast cancer-Extending adjuvant hormone therapy beyond tamoxifen • Goss PE et al. N Engl J Med 349: 1793-802, 2003 As compared with placebo, letrozole after the completion of standard tamoxifen significantly improves DFS. (See also updated report: Goss PE et al. J Natl Cancer Inst 97: 1262-71, 2005) • Coombes RC et al. N Engl J Med 350: 1081-92, 2004 Exemestane therapy after 2 to 3 years of tamoxifen significantly improved DFS as compared with the standard 5 yrs of tamoxifen (see follow-up: Coombes RC et al. Lancet 369: 559-70, 2007). • Boccardo F et al. J Clin Oncol 22: 5138-47, 2005 Anastrazole after 2 to 3 years of tamoxifen significantly improved DFS as compared with the standard 5 yrs of tamoxifen (see also editorial: Pritchard KI. J Clin Oncol 22: 4850-2, 2005)

  37. Letrozole vs tamoxifen as adjuvant • The Breast International Group (BIG 1-98 Group. N Engl J Med 353: 2747-57, 2005: Compared with tamoxifen, letrozole reduced the risk of recurrent disease, especially at distant sites. • Coates A et al. J Clin Oncol 25: 486-92, 2007 (update of BIG 1-98): Confirm the initial results. 18% reduction in the risk of an event; different spectrum of adverse effects.

  38. Herceptin chemotherpy and as single agent • Slamon DJ et al. N Engl J Med 344: 783-792, 2001 Herceptin increases the clinical benefit of first-line chemotherapy in MBC that overexpress HER 2. • Vogel CL et al. J Clin Oncol 20: 719-26, 2002 Single agent herceptin is active and well tolerated (objective response rate 26%; 34% in FISH positive).

  39. Herceptin every 3 weeks • Leyland-Jones B et al. J Clin Oncol 21: 3965-71, 2003 Herceptin every 3 weeks in combination with paclitaxel is generally well tolerated. Additional investigation of this schedule is warranted. See also editorial: • Cobleigh M and Frame D. J Clin Oncol 21: 3900-1, 2003

  40. Herceptin as adjuvant therapy- randomized trials • Piccart-Gebhart M et al. N Engl J Med 353: 1659-72, 2005 (HERA= herceptin adjuvant): (Herceptin every 3 wks was given for one or two years after locoregional therapy) (see also: Smith I et al. Lancet 369: 29-36, 2007; 2-year follow-up showing survival benefit for 1 year of treatment with herceptin). • Romond EH et al. N Engl J Med 353: 1673-84, 2005 (NSABP B-31 & Intergoup N9831): Herceptin weekly for one year initiated after AC+ paclitaxel adjuvant therapy or concomitantly with paclitaxel). • Joensuu H et al. N Engl J Med 354: 809-20, 2006 (FinHer=Finish trial): Herceptin was given for 9 weeks in combination with docetaxel or vinorelbine. • Smith I et al. Lancet. 2007, 6;369:29-36: 2 yrs follow-up: 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years.

  41. HER2 and responsiveness of breast cancer to adjuvant chemotherapy • Pritchard KI et al. N Engl J Med 354: 2103-11, 2006: Amplification of HER2 in breast-cancer cells is associated with a larger benefit from CEF (cyclophosphamide, epirubicin, 5FU), as compared with CMF.

  42. ASCO technology assessment of the use of aromatase inhibitors • Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment of the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23: 619-29, 2005

  43. Colorectal cancer • Bevacizumab (avastin) in metastatic colorectal cancer…. • Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer…. • Cetuximab & Cetuximab plus irinotecan in irinotecan-refractory MCRC…. • ASCO recommendations on adjuvant chemotherapy for stage II colon cancer…. • Capecitabine as adjuvant in stage III (X-ACT)…. • Chemotherapy with preoperative radiotherapy in rectal cancer….

  44. Bevacizumab (avastin) in metastatic colorectal cancer • Kabbinavar F et al. J Clin Oncol 21: 60-5, 2003 A phase II randomized study that compared 5FU/LCV to 5FU/LCV+ avastin as first-line in MCRC. “...encouraging results…” • Hurwitz H et al. N Engl J Med 350: 2335-42, 2004: Addition of avastin to standard IFL (irinotecan, 5FU, leucovorin) in MCRC improved response rate, progression free survival, and survival. • Kabbinavar FF et al. J Clin Oncol 23: June 1, 2005: The addition of bevacituzumab to FU/LV provides a statistically significant and clinically relevant benefit in pts with previously untreated CRC.

  45. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer • Andre T et al. N Engl J Med 350: 2343-51, 2004 (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer=MOSAIC) Adding oxaliplatin to a regimen of 5FU/LCV improves the adjuvant treatment of colon cancer.

  46. Cetuximab & Cetuximab plus irinotecan in irinotecan-refractory MCRC • Cunnigham D et al. N Engl J Med 351:337-45, 2004 Cetuximab has clinically significant activity when given alone or in combination with irinotecan in pts with irinotecan-refractory CRC.

  47. ASCO recommendations on adjuvant chemotherapy for stage II colon cancer • Benson III AlB et al. J Clin Oncol 22: 3408-19, 2004

  48. Capecitabine as adjuvant in stage III (X-ACT) • Twelves C et al. N Engl J Med 352: 2696-2704, 2005 Capecitabine is at least equivalent to the Mayo Clinic regimen (better DFS & less toxicity.

  49. Chemotherapy with preoperative radiotherapy in rectal cancer • Bosset JF et al. N Engl J Med 355: 1114-23, 2006 In pts with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemopre or post operatively has no significant effect on survival. Chemotherapy (whether pre or post op.) confers a significant benefit with respect to local control.

  50. Gastric cancer • Chemoraio after surgery vs surgery alone (Macdonald JS et al, NEJM,2001)…. • Perioperative chemo (ECF) vs. surgery alone in resectable gastrointestinal cancer (MAGIC)….

More Related